Phase I Trial of the Combination of Zidovudine and Recombinant Interleukin-2 in Patients With Persistent Generalized Lymphadenopathy

This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Stanford,
California94305

Purpose:

To evaluate the short-term effects of administering zidovudine ( AZT ) at the same time with
increasing doses of aldesleukin ( interleukin-2; IL-2 ) in patients with persistent
generalized lymphadenopathy syndrome ( PGL ). The effects to be studied include safety or
toxicity, how quickly the drugs are used in the body, effects on the immune system, effects
on HIV, concentrations in body fluids, and how quickly the drugs are cleared by the kidneys.
The trial will establish the maximum tolerated dose ( MTD ) and will be a pilot study to
determine the dose that has the greatest effect in the immune system.
AZT has been shown to be effective in HIV-related disease. IL-2 has been shown to increase
immune responses and correct immune problems caused by HIV in the test tube. IL-2 has also
been effective in treating Kaposi's sarcoma in a number of patients. Because of the clinical
activities of these two drugs and because their toxicities and mechanisms of action do not
overlap, it may be beneficial to combine the two drugs with their antiviral and immune
stimulatory effects.

Study summary:

AZT has been shown to be effective in HIV-related disease. IL-2 has been shown to increase
immune responses and correct immune problems caused by HIV in the test tube. IL-2 has also
been effective in treating Kaposi's sarcoma in a number of patients. Because of the clinical
activities of these two drugs and because their toxicities and mechanisms of action do not
overlap, it may be beneficial to combine the two drugs with their antiviral and immune
stimulatory effects.
Patients enter the study in staggered groups of five. All patients receive AZT orally every
4 hours for 12 weeks. At the end of 8 weeks, the first group of five patients receive the
lowest dosage of IL-2 on a daily basis while still receiving AZT. Toxicity and immunologic
effects are measured at the beginning of AZT therapy and then every 2 weeks. Each succeeding
group of five patients receives a higher dose of IL-2, while receiving AZT, until the MTD is
reached. Those patients who have shown no toxicity as well as improved immune function while
taking both drugs receive a 4-week follow-up course of IL-2 5 weeks after stopping AZT. In
addition, five patients who have completed the AZT / IL-2 combined treatment without
significant toxicity are re-treated with 12 weeks of AZT alone starting 8 weeks after
completing the initial combined AZT / IL-2 portion of treatment. Another five patients will
be re-treated with 12 weeks of full dose of AZT alone, followed by 8 weeks of half-dose AZT
alone starting 8 weeks after completing the initial combined AZT / IL-2 treatment. Patients
receive ibuprofen for fever and chills, and those who reach their MTD continue to receive
that dose in combination with AZT for 4 weeks. If excess toxicity is observed on all doses
of IL-2, the study will be discontinued.

Criteria:

Inclusion Criteria
- Detectable HIV nucleic acid in patient peripheral blood mononuclear leukocytes
(PBML's) by the gene amplification technique. A positive antibody to HIV confirmed by
any federally licensed ELISA test kit.
Concurrent Medication:
Allowed:
- Medications without which there might be significant risk, such as seizures, loss of
diabetic control or respiratory embarrassment.
- Necessary topical agents including topical acyclovir.
- Diuretics for significant fluid retention only.
Concurrent Treatment:
Allowed:
- Blood transfusions for anemia if hematocrit falls below 25 percent.
Exclusion Criteria
- Active drug or alcohol abuse.
Co-existing Condition:
Patients with the following will be excluded:
- Grade 1 impairment on two or more items in the ACTG Micro Neuro AIDS assessment.
- Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma
of the cervix.
- Major organ allograft.
- Significant cardiac disease or central nervous system lesions.
- Patients with hemophilia should be evaluated and treated under the hemophilia
protocol.
Concurrent Medication:
Excluded:
- Inderal or vasoactive hypertensive medication.
- Non-essential medications including pain medications.
Excluded are:
- Patients with an opportunistic infection or malignancy fulfilling the definition of
AIDS.
Patients with AIDS related complex, defined as:
- 1. Weight loss in excess of 15 lbs. or 10 percent of body weight noted in a 2-year
period prior to entry into the study. 2. Temperature greater than 38.5 degrees C with
or without night sweats, persisting for more than 14 consecutive days or more than 15
days in a 30-day interval during a 2-year period prior to entry into the study. 3.
Diarrhea defined as = or > 3 liquid stools per day, persisting for more than 30 days
during a 2-year period prior to entry into the study without a definable cause. 4.
Herpes zoster during the past 2 years. 5. Oral candidiasis or biopsy-proven hairy
leukoplakia during the last 2 years. 6. Active substance abuse.
Prior Medication:
Excluded:
- Zidovudine (AZT).
- Excluded within 30 days of study entry:
- Antiretroviral agents.
- Biologic response modifiers.
- Corticosteroids.
- Excluded within 60 days of study entry:
- Ribavirin.

NCT ID:

NCT00000728

Primary Contact:

Study ChairMerigan TC

Backup Contact:

N/A

Location Contact:

Stanford, California 94305United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: June 25, 2018

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.